RGD Reference Report - Impact of angiotensin II type 2 receptor blockade on experimental radiation nephropathy. - Rat Genome Database

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Impact of angiotensin II type 2 receptor blockade on experimental radiation nephropathy.

Authors: Moulder, JE  Fish, BL  Cohen, EP 
Citation: Moulder JE, etal., Radiat Res. 2004 Mar;161(3):312-7.
RGD ID: 6903857
Pubmed: (View Article at PubMed) PMID:14982483

In the rat, blockade of angiotensin II type 1 receptors diminishes the functional changes that occur after kidney irradiation. It has been hypothesized that some of the beneficial effects of angiotensin II type 1 blockers in renal disease are caused by a rise in angiotensin II that stimulates the angiotensin II type 2 receptor. If this hypothesis applied in this model, blockade of the type 2 receptor should exacerbate radiation nephropathy and/or counteract the beneficial effects of type 1 receptor blockade. To assess this hypothesis, rats were given total-body irradiation plus bone marrow transplantation and then treated for 12 weeks with a type 1 receptor blocker (L158,809), a type 2 blocker (PD123319), both blockers, or no blockers. Rats were assessed for renal function (proteinuria, hypertension, azotemia) and renal failure for up to 62 weeks. Contrary to the hypothesis, the type 2 blocker alone produced a temporary delay in the development of radiation nephropathy, and it substantially enhanced the efficacy of the type 1 blocker. This implies that both type 1 and type 2 angiotensin receptors need to be blocked to achieve the maximum level of prophylaxis of radiation nephropathy. We speculate that the beneficial effect of the angiotensin II type 2 receptor blocker is due to a reduction in radiation-induced renal cell proliferation or fibrosis.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr2  (angiotensin II receptor, type 2)

Genes (Mus musculus)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr2  (angiotensin II receptor, type 2)

Genes (Homo sapiens)
AGTR1  (angiotensin II receptor type 1)
AGTR2  (angiotensin II receptor type 2)


Additional Information